Cisplatin Adverse Reaction, Vomiting
Conditions
Keywords
Vomiting, Antiemetics, Dexamethasone, Cisplatin, Antineoplastic combined chemotherapy protocols
Brief summary
Gabapentin is an antiepileptic drug. Its antiemetic effect is demonstrated after laparoscopic surgery, but it is not yet known whether gabapentin is effective in preventing chemotherapy induced emesis. The purpose of this study is to determine whether the addition of gabapentin to dexamethasone plus ondansetron increase the control of chemotherapy-induced nausea and vomiting.
Detailed description
This was a prospective, double-blind, placebo-controlled study conducted at our institution (Faculdade de Medicina da Fundação ABC and affiliated Hospitals) from April 2009 to April 2010. Patients and personnel involved in the study were blinded to the assigned treatment. The study was approved by the ethics committee of our institution. All the patients provided written informed consent.
Interventions
DRUGPlacebo
Placebo, given orally Ranitide 50 mg, IV, before chemotherapy (D1) Ondansetron 8 mg, IV, before chemotherapy (D1) Dexamethasone 10 mg, IV, before chemotherapy (D1) Dexamethasone 4 mg, PO, 2x/day (D2, D3)
DRUGGabapentin
Gabapentin 300mg, orally Ranitide 50 mg, IV, before chemotherapy (D1) Ondansetron 8 mg, IV, before chemotherapy (D1) Dexamethasone 10 mg, IV, before chemotherapy (D1) Dexamethasone 4 mg, PO, 2x/day (D2, D3)
Sponsors
Faculdade de Medicina do ABC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* First course of chemotherapy ( cisplatin or doxorubicin at a dose of at least 50mg per square meter) * Written informed consent must be obtained before initiating the protocol procedures
Exclusion criteria
* ECOG 3 * Nausea and vomiting within the past 1 day * Gastrointestinal obstruction * Concurrent use of opioid * Patients with brain metastases * History of allergic or other adverse reaction to gabapentin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Complete Response During Chemotherapy Course 1 | 5 days | The CR was defined as no emetic episodes and no nausea episodes from day 1 to day 5 (0-120h) |
| Number of Patients With CR During Delayed-onset Phase (24-120 Hours) After Administration of Chemotherapy Course 1 | 6 days | Complete response during delayed-onset phase was defined as the absence of any episode of nausea or vomiting and no use of rescue medication when occurring during the period from days 2 through 5 after chemotherapy |
Countries
Brazil
Participant flow
Recruitment details
This was a prospective, double-blind, placebo-controlled study conducted at our institution (Faculdade de Medicina da Fundação ABC and affiliated Hospitals) from April 2009 to April 2010. Patients and personnel involved in the study were blinded to the assigned treatment.
Pre-assignment details
Patients and personnel involved in the study were blinded to the assigned treatment. The study was approved by the ethics committee of our institution. All the patients provided written informed consent. No enrolled participants were excluded from the trial.
Participants by arm
| Arm | Count |
|---|---|
| Control Group Dexamethasone 10mg + Ondansetron 8mg + Ranitidine 50mg , IV, before chemotherapy infusion (D1)
Dexamethasone 8mg orally 24h (day 2) and 48h (day 3) after chemotherapy
Placebo:
* Five and four days before chemotherapy (day -5 and day -4): 1x daily
* Three and two days before chemotherapy (day -3 and day -2): 2x daily
* One day before to five days after chemotherapy ( day -1 to day 5): 3x daily | 40 |
| Gabapentin Dexamethasone 10mg + Ondansetron 8mg + Ranitidine 50mg , IV, before chemotherapy infusion (D1)
Dexamethasone 8mg orally 24h (day 2) and 48h (day 3) after chemotherapy
Gabapentin 300mg:
* Five and four days before chemotherapy (day -5 and day -4): 1x daily
* Three and two days before chemotherapy (day -3 and day -2): 2x daily
* One day before to five days after chemotherapy ( day -1 to day 5): 3x daily | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Gabapentin | Control Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 6 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants | 34 Participants | 68 Participants |
| Age, Continuous | 55.6 years STANDARD_DEVIATION 9.9 | 52.3 years STANDARD_DEVIATION 10.4 | 53.9 years STANDARD_DEVIATION 10.2 |
| Region of Enrollment Brazil | 40 participants | 40 participants | 80 participants |
| Sex: Female, Male Female | 36 Participants | 39 Participants | 75 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 40 | 23 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 |
Outcome results
Primary
Number of Patients With Complete Response During Chemotherapy Course 1
The CR was defined as no emetic episodes and no nausea episodes from day 1 to day 5 (0-120h)
Time frame: 5 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Group | Number of Patients With Complete Response During Chemotherapy Course 1 | 17 participants |
| Gabapentin | Number of Patients With Complete Response During Chemotherapy Course 1 | 26 participants |
Comparison: Complete protection from nausea and vomiting (CP) was defined as the absence of any episode of nausea or vomiting and no use of rescue medication. CP was further defined as either acute (ACP), when occurring during the first 24 hours after chemotherapy; delayed (DCP), when occurring during the period from days 2 through 5 after chemotherapy; or overall, when occurring over the entire period of the study (first 120 hours).p-value: 0.04Chi-squared
Primary
Number of Patients With CR During Delayed-onset Phase (24-120 Hours) After Administration of Chemotherapy Course 1
Complete response during delayed-onset phase was defined as the absence of any episode of nausea or vomiting and no use of rescue medication when occurring during the period from days 2 through 5 after chemotherapy
Time frame: 6 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Group | Number of Patients With CR During Delayed-onset Phase (24-120 Hours) After Administration of Chemotherapy Course 1 | 21 participants |
| Gabapentin | Number of Patients With CR During Delayed-onset Phase (24-120 Hours) After Administration of Chemotherapy Course 1 | 29 participants |
Comparison: We evaluated associations between categorical variables using the Chi-Square testp-value: 0.06Chi-squared